DISCOVER-2 post hoc analysis: Guselkumab in biologic-naïve patients with PsA and severe disease activity

In patients with active psoriatic arthritis (PsA) who are biologic-naïve, the phase III DISCOVER-2 trial (NCT03158285) demonstrated that guselkumab significantly improved PsA signs and symptoms compared with placebo, with clinical benefits observed by 6 months and maintained through 2 years.

A post hoc analysis of the DISCOVER-2 trial evaluated the efficacy of guselkumab through Week 100 in 739 patients with active PsA. The three cohorts analyzed included subgroups of patients with severe disease activity at baseline, defined as clinical Disease Activity Index for Psoriatic Arthritis (cDAPSA) >27 (n = 648), Psoriatic Arthritis Disease Activity Score (PASDAS) ≥ 5.4 (n = 639), and patient global assessment (PtGA) Arthritis + Psoriasis ≥ 80 mm (n = 218). Results were published by Ritchlin et al. in Rheumatology and Therapy.¹ 

Key learnings

Guselkumab Q4W and Q8W showed greater LSM differences vs placebo in the cDAPSA cohort at Week 2 (−5.9 [p = 0.3905] and −7.2 [p = 0.0379]), and PASDAS (−1.5 for both; p < 0.0001) and PtGA cohorts (−30.0, −32.1; both p < 0.01) at Week 8.

The change in LSM from baseline through Week 24 increased with guselkumab Q4W and Q8W vs placebo in the cDAPSA (−9.8 and −9.0), PASDAS (−1.1 for both), and PtGA cohorts (−24.0 and −20.2; all p < 0.0001).

Sustained improvements with greater LSM change from baseline were observed with guselkumab Q4W and Q8W through Week 100 in the cDAPSA (−35.9 and −35.6), PASDAS (−3.6 and −3.7), and PtGA cohorts (−56.8 and −55.5).

Guselkumab is efficacious in achieving early (Weeks 2/8) and durable (sustained through 2 years) improvements across multiple key PsA domains in biologic-naïve patients with PsA and severe disease activity, as defined by both physician-assessed and patient-reported components commonly used in the real-world settings.